The Prognostic Analysis Of Continued EGFR-TKI Plus Local Therapy In Non-small Cell Lung Cancer Patients With Acquired Resistance

Objective: Lung cancer is one of the malignant tumors with the highest morbidity and mortality in China and around the world.Non-small cell lung cancer(NSCLC)accounts for about 80% of the cases.For patients with advanced or metastatic non-small cell lung cancer with epidermal growth factor receptor(EGFR)sensitive mutations,epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)effectively improve survival outcomes.However,despite the improved efficacy of EGFR-TKIs compared with that of systemic chemotherapy,patients would eventually develop acquired resistance after 9-14 months of the first-or second-generation EGFR-TKI treatment.We conducted a single-arm retrospective study to explore the efficacy of continued original EGFR-TKI with local therapy upon the acquired resistance of the first-or secondgeneration EGFR-TKI.Methods: NSCLC patients with EGFR activating mutations who were treated at the First Affiliated Hospital of China Medical University from August 2013 to August 2019 were collected.Response Evaluation Criteria in Solid Tumours(RECIST,version 1.1)was used to assess the efficacy.PFS1 was defined as the patient's progression-free survival(PFS)from the acquisition of EGFR-TKI treatment to the emergence of drug resistance;PFS2 was defined as the progression-free survival from the initiation of continued original EGFR-TKI with local therapy to the second progression;PFS was defined as PFS1 + PFS2.Statistical analyses were performed using SPSS software.Kaplan-Meier curve and log-rank test were used to analyse the difference between PFS(PFS1 + PFS2)and PFS1.P < 0.05 was considered statistically significant.The factors that may affect PFS were analysed by univariate and multivariate analysis using Cox proportional hazard regression model.Considering that the number of patients in this study was relatively small,in the univariate analysis,the variables that reached P < 0.1 or that we considered worthy of attention in clinical practice were included in the multivariate analysis model.In the univariate and multivariate analysis,P < 0.05 was considered statistically significant.All P values were two-tailed.Results: Thirty-three patients were deemed eligible and were collected.The median PFS1,median PFS2,and median PFS of the 33 patients were 10 months(range,1-32),4 months(1-42),and 15 months(5-51).Log-rank analysis showed that P = 0.013 < 0.05,which indicated a statistically significant difference between PFS and PFS1.The results of the univariate analysis showed that the variables that reached statistical significance were: ECOG score(0-1 vs.2)(HR = 0.062,95% confidence interval(95% CI): 0.006-0.689,P = 0.024)and whether the primary tumor was surgically removed(Yes vs.No)(HR = 0.270,95% CI: 0.120-0.607,P = 0.002).Only whether the primary tumor was surgically removed(Yes vs.No)remained significant(HR = 0.307,95% CI: 0.132-0.713,P = 0.006)adjusted by the Cox multivariate regression model.Conclusion: Continued EGFR-TKI plus local therapy could provide additional benefits to EGFR-mutant NSCLC patients upon acquired resistance.However,due to the singlearm nature of this retrospective study,this result should be interpreted cautiously and needs to be further validated by well-designed large-scale randomized controlled trials.